Management of fetal head and neck masses: Evaluation of prenatal factors associated with airway obstruction and decision for definitive airway and ex-utero intrapartum treatment at birth.

OBJECTIVE: Fetal head and neck masses can result in critical airway obstruction. Our study aimed to evaluate prenatal factors associated with the decision for a definitive airway, including ex-utero intrapartum treatment (EXIT), at birth among at-risk fetuses. METHODS: A single-institution retrospective review evaluated all fetal head and neck masses prenatally diagnosed from 2005 to 2023. The primary outcome was the decision for a definitive airway at birth, including intubation, tracheostomy, or EXIT. RESULTS: Thirty four patients were included, with 23 deliveries occurring at our institution. 8/23 (35%) patients received a definitive airway at birth, six underwent an EXIT procedure, and two required intubation only. Patients who received a definitive airway had higher rates of polyhydramnios (50% vs. 7%, p = 0.03), tracheal narrowing on ultrasound (US) (50% vs. 0%, p = 0.01), tracheal displacement on US (63% vs. 0%, p < 0.01), abnormal fetal breathing on US (50% vs. 0%, p = 0.01), tracheal narrowing or displacement on magnetic resonance imaging (MRI) (75% vs. 7%, p < 0.01), and larger mass maximum diameter (7.9 vs. 4.3 cm, p = 0.02). In our series, 100% of patients with polyhydramnios, tracheal narrowing or displacement on either US or MRI, and abnormal fetal breathing on US received a definitive airway at birth. CONCLUSION: Prenatal findings of tracheal narrowing or displacement, polyhydramnios, and abnormal fetal breathing are strongly associated with the decision for a definitive airway at birth and warrant mobilization of appropriate resources.

Uterus and cervix anatomical changes and cervix stiffness evolution throughout pregnancy.

The coordinated biomechanical performance, such as uterine stretch and cervical barrier function, within maternal reproductive tissues facilitates healthy human pregnancy and birth. Quantifying normal biomechanical function and detecting potentially detrimental biomechanical dysfunction (e.g., cervical insufficiency, uterine overdistention, premature rupture of membranes) is difficult, largely due to minimal data on the shape and size of maternal anatomy and material properties of tissue across gestation. This study quantitates key structural features of human pregnancy to fill this knowledge gap and facilitate three-dimensional modeling for biomechanical pregnancy simulations to deeply explore pregnancy and childbirth. These measurements include the longitudinal assessment of uterine and cervical dimensions, fetal weight, and cervical stiffness in 47 low-risk pregnancies at four time points during gestation (late first, middle second, late second, and middle third trimesters). The uterine and cervical size were measured via 2-dimensional ultrasound, and cervical stiffness was measured via cervical aspiration. Trends in uterine and cervical measurements were assessed as time-course slopes across pregnancy and between gestational time points, accounting for specific participants. Patient-specific computational solid models of the uterus and cervix, generated from the ultrasonic measurements, were used to estimate deformed uterocervical volume. Results show that for this low-risk cohort, the uterus grows fastest in the inferior-superior direction from the late first to middle second trimester and fastest in the anterior-posterior and left-right direction between the middle and late second trimester. Contemporaneously, the cervix softens and shortens. It softens fastest from the late first to the middle second trimester and shortens fastest between the late second and middle third trimester. Alongside the fetal weight estimated from ultrasonic measurements, this work presents holistic maternal and fetal patient-specific biomechanical measurements across gestation.

Parametric Solid Models of the At-Term Uterus From Magnetic Resonance Images.

Birthing mechanics are poorly understood, though many injuries during childbirth are mechanical, like fetal and maternal tissue damage. Several biomechanical simulation models of parturition have been proposed to investigate birth, but many do not include the uterus. Additionally, most solid models rely on segmenting anatomical structures from clinical images to generate patient geometry, which can be time-consuming. This work presents two new parametric solid modeling methods for generating patient-specific, at-term uterine three-dimensional geometry. Building from an established method of modeling the sagittal uterine shape, this work improves the uterine coronal shape, especially where the fetal head joins the lower uterine wall. Solid models of the uterus and cervix were built from five at-term patients' magnetic resonance imaging (MRI) sets. Using anatomy measurements from MRI-segmented models, two parametric models were created-one that employs an averaged coronal uterine shape and one with multiple axial measurements of the coronal uterus. Through finite element analysis, the two new parametric methods were compared to the MRI-segmented high-fidelity method and a previously published elliptical low-fidelity method. A clear improvement in the at-term uterine shape was found using the two new parametric methods, and agreement in principal Lagrange strain directions was observed across all modeling methods. These methods provide an effective and efficient way to generate three-dimensional solid models of patient-specific maternal uterine anatomy, advancing possibilities for future research in computational birthing biomechanics.

Outcomes associated with peripartum hysterectomy in the setting of placenta accreta spectrum disorder.

BACKGROUND: Although peripartum hysterectomy for placenta accreta spectrum disorder is known to be associated with complications at the time of delivery, there are limited data on postpartum outcomes and readmission risk in this population. OBJECTIVE: This study aimed to analyze risks for adverse outcomes and postpartum readmissions in the setting of peripartum hysterectomy for placenta accreta spectrum disorder by severity of placenta accreta spectrum disorder subcategory. STUDY DESIGN: Using the 2016-2020 Nationwide Readmissions Database, this retrospective cohort study identified peripartum hysterectomies with a diagnosis of placenta accreta spectrum disorder. The primary exposure was placenta accreta spectrum disorder, subcategorized as placenta accreta vs increta/percreta. The primary outcome was readmission rate and delivery complications. Complications evaluated included the following: (1) nontransfusion severe maternal morbidity (ntSMM), (2) venous thromboembolism, (3) reoperation, (4) intraoperative complications, (5) hemorrhage, (6) sepsis, and (7) surgical site complications. We additionally evaluated delivery hospitalization and readmission mean length of stay, and hospital costs. Unadjusted and adjusted logistic regression models were fit for outcomes adjusting for clinical, demographic, and hospital factors. The association measures were expressed as unadjusted and adjusted odds ratios with 95% confidence intervals. RESULTS: Between 2016 and 2020, 7864 hysterectomies during a delivery hospitalization with a diagnosis of placenta accreta spectrum disorder were identified (66.5% with placenta accreta and 33.5% with placenta increta/percreta diagnoses). The overall 60-day all-cause readmission rate was 7.3%. Most readmissions (57.2%) occurred within 10 days of hospital discharge. Compared with peripartum hysterectomy with a diagnosis of placenta accreta, hysterectomies with placenta increta/percreta diagnoses carried significantly increased risk of 60-day readmission (adjusted odds ratio, 1.31; 95% confidence interval, 1.01-1.71), inpatient mortality (odds ratio, 13.23; 95% confidence interval, 3.35-52.30), nontransfusion severe maternal morbidity (adjusted odds ratio, 1.43; 95% confidence interval, 1.20-1.71), intraoperative complications (adjusted odds ratio, 2.31; 95% confidence interval, 1.93-2.77), and surgical site complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.23-1.95). The median length of stay during delivery hospitalization was longer for placenta increta/percreta (5.8 days; 95% confidence interval, 5.4-6.1) than for placenta accreta (4.2 days; 95% confidence interval, 4.1-4.3; P<.05). In addition, delivery hospitalization costs were higher in cases of placenta increta/percreta (median, $30,686; 95% confidence interval, $28,922-$32,449) than placenta accreta (median, $21,321; 95% confidence interval, $20,480-$22,163). CONCLUSION: Complication and readmission risks after peripartum hysterectomy with placenta accreta spectrum disorder are high. Compared with patients with placenta accreta, patients with placenta increta/percreta had increased risk for delivery and postoperative complications and postpartum readmission, and increased costs and length of stay.

Investigation into the genetics of fetal congenital lymphatic anomalies.

OBJECTIVE: Congenital lymphatic anomalies (LAs) arise due to defects in lymphatic development and often present in utero as pleural effusion, chylothorax, nuchal and soft tissue edema, ascites, or hydrops. Many LAs are caused by single nucleotide variants, which are not detected on routine prenatal testing. METHODS: Demographic data were compared between two subcohorts, those with clinically significant fetal edema (CSFE) and isolated fetal edema. A targeted variant analysis of LA genes was performed using American College of Medical Genetics criteria on whole exome sequencing (WES) data generated for 71 fetal edema cases who remained undiagnosed after standard workup. RESULTS: CSFE cases had poor outcomes, including preterm delivery, demise, and maternal preeclampsia. Pathogenic and likely pathogenic variants were identified in 7% (5/71) of cases, including variants in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant. Variants of uncertain significance (VOUS) were identified in 45% (32/71) of cases. In CSFEs, VOUS were found in CELSR1, EPHB4, TIE1, PIEZO1, ITGA9, RASopathy genes, SOS1, SOS2, and RAF1. CONCLUSIONS: WES identified pathogenic and likely pathogenic variants and VOUS in LA genes in 51% of fetal edema cases, supporting WES and expanded hydrops panels in cases of idiopathic fetal hydrops and fluid collections.

Prenatal weight and regional body composition trajectories and neonatal body composition: The NICHD Foetal Growth Studies.

BACKGROUND: Gestational weight gain (GWG) and anthropometric trajectories may affect foetal programming and are potentially modifiable. OBJECTIVES: To assess concomitant patterns of change in weight, circumferences and adiposity across gestation as an integrated prenatal exposure, and determine how they relate to neonatal body composition. METHODS: Data are from a prospective cohort of singleton pregnancies (n = 2182) enrolled in United States perinatal centres, 2009-2013. Overall and by prepregnancy BMI group (overweight/obesity and healthy weight), joint latent trajectory models were fit with prenatal weight, mid-upper arm circumference (MUAC), triceps (TSF) and subscapular (SSF) skinfolds. Differences in neonatal body composition by trajectory class were assessed via weighted least squares. RESULTS: Six trajectory patterns reflecting co-occurring changes in weight and MUAC, SSF and TSF across pregnancy were identified overall and by body mass index (BMI) group. Among people with a healthy weight BMI, some differences were observed for neonatal subcutaneous adipose tissue, and among individuals with overweight/obesity some differences in neonatal lean mass were found. Neonatal adiposity measures were higher among infants born to individuals with prepregnancy overweight/obesity. CONCLUSIONS: Six integrated trajectory patterns of prenatal weight, subcutaneous adipose tissue and circumferences were observed that were minimally associated with neonatal body composition, suggesting a stronger influence of prepregnancy BMI.

Prophylactic endovascular internal iliac balloon placement during cesarean hysterectomy for placenta accreta spectrum.

BACKGROUND: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated. OBJECTIVE: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution. STUDY DESIGN: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test. RESULTS: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36). CONCLUSION: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time.

Characterization of amniotic fluid sludge in preterm and term gestations.

OBJECTIVE: To describe the characteristics of amniotic fluid sludge obtained from patients in term and preterm gestations. METHODS: This cross-sectional study included patients with dense aggregates of particulate matter detected in amniotic fluid, observed with transvaginal sonography. All patients were in labor and had an impending delivery, either preterm or at term. Echogenic material contained within amniotic fluid was retrieved transvaginally by needle amniotomy under direct visualization. The amniotic fluid analysis consisted of a Gram stain, cultures for aerobic/anaerobic bacteria and genital mycoplasmas, and a white blood cell count. RESULTS: Twenty-five patients ranging from 18 to 41 weeks of gestation were included in the study. We observed the following: (1) the appearance of amniotic fluid was consistent with pus-like material, vernix, or meconium by naked eye examination; (2) samples collected before 33 weeks of gestation (n = 13) had a pus-like appearance; however, after this gestational age, most of the samples [83% (10/12)] appeared to be consistent with vernix; (3) amniotic fluid cultures were positive for microorganisms in 13 patients, of which 10 were preterm gestations before 33 weeks; (4) the most frequent microorganisms retrieved by culture were genital mycoplasmas (Ureaplasma urealyticum [46% (6/13)]), followed by Mycoplasma hominis [31% (4/13)] and Candida albicans [15% (2/13)]; and (5) patients with sonographic particulate matter in preterm gestations frequently presented acute histologic chorioamnionitis and funisitis, but these conditions were rare in patients at term. CONCLUSION: The nature of amniotic fluid particulate material varies as a function of gestational age. The material obtained in preterm gestations is frequently related to an inflammatory process, while that obtained at term is often consistent with vernix and appears to represent a maturational process.

Sleep-disordered Breathing in Pregnancy and after Delivery: Associations with Cardiometabolic Health.

Rationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2) oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).

The role of fetal echocardiogram after detection of extracardiac anomalies in utero (fetal echocardiogram for extracardiac malformations).

OBJECTIVE: We aimed to investigate the utility of comprehensive screening fetal echocardiography (FE) for patients diagnosed with any type of fetal extracardiac malformation (ECM) at a single multidisciplinary fetal center. METHODS: We retrospectively reviewed all patients presenting to our referral center for FE due to a prenatal diagnosis of ECM (January 2013-December 2018). RESULTS: Among 641 patients with ≥1 ECM referred for FE, 78 (12.2%) had CHD diagnosed at 25.6 ± 0.5 weeks. The frequency of CHD by type of ECM ranged from 35.1% for craniofacial to 9.8% for thoracic. Increasing number of fetal ECMs was strongly associated with CHD: odds ratio 2.01 (95% confidence interval: 1.06-3.69) for two ECMs, 9.57 (2.00-49.05) for three ECMs, and 11.68 (3.84-37.15) for more than three ECMs. Of fetuses with ECM and an abnormal genetic finding, 33.3% had CHD as compared to 10.9% of those without (p < 0.0001). Obstetric anatomy sonogram detected 43.6% of CHD. CONCLUSION: CHD was commonly diagnosed among fetuses with any type of ECM at our center but was not always detected on obstetric sonogram. As the presence of CHD may impact decision-making and perinatal care, patients with a diagnosis of any fetal ECM should be considered for FE.

Objectively assessed sleep-disordered breathing during pregnancy and infant birthweight.

BACKGROUND: Sleep-disordered breathing (SDB) in pregnancy is associated with adverse maternal outcomes. The relationship between SDB and infant birthweight is unclear. This study's primary aim is to determine if objectively measured SDB in pregnancy is associated with infant birthweight. METHODS: We measured SDB objectively in early (6-15 weeks' gestation) and mid (22-31 weeks' gestation) pregnancy in a large cohort of nulliparous women. SDB was defined as an Apnea-Hypopnea Index ≥5 and in secondary analyses we also examined measures of nocturnal hypoxemia. We used a modified Poisson regression approach to estimate relative risks (RR) of large-for-gestational-age (LGA: >90th percentile for gestational age) and small-for-gestational-age (SGA: <10th percentile for gestational age) birthweights. RESULTS: The prevalence of early-pregnancy SDB was nearly 4%. The incidence of mid-pregnancy SDB was nearly 6.0%. The prevalence of LGA and SGA was 7.4% and 11.9%, respectively. Early-pregnancy SDB was associated with a higher risk of LGA in unadjusted models (RR 2.2, 95% CI 1.3-3.5) but not BMI-adjusted models (aRR 1.0, 95% CI 0.6-1.8). Mid-pregnancy SDB was not associated with SGA or LGA. Mid-pregnancy nocturnal hypoxemia (% of sleep time <90% oxygen saturation) and increasing nocturnal hypoxemia from early to mid-pregnancy were associated with a higher risk of LGA in BMI-adjusted models. SDB and nocturnal hypoxemia were not associated with SGA. CONCLUSIONS: SDB in pregnancy was not associated with an increased risk of LGA or SGA birthweight, independent of BMI. Some measures nocturnal hypoxemia were associated with an increase in LGA risk, independent of BMI. ClinicalTrials.gov Registration number NCT02231398.

Adaptation of prenatal care and ultrasound.

In the spring of 2020, expeditious changes to obstetric care were required in New York as cases of COVID-19 increased and pandemic panic ensued. A reduction of in-person office visits was planned with provider appointments scheduled to coincide with routine maternal blood tests and obstetric ultrasounds. Dating scans were combined with nuchal translucency assessments to reduce outpatient ultrasound visits. Telehealth was quickly adopted for selected prenatal visits and consultations when deemed appropriate. The more sensitive cell-free fetal DNA test was commonly used to screen for aneuploidy in an effort to decrease return visits for diagnostic genetic procedures. Antenatal testing guidelines were modified with a focus on providing evidence-based testing for maternal and fetal conditions. For complex pregnancies, fetal interventions were undertaken earlier to avoid serial surveillance and repeated in-person hospital visits. These rapid adaptations to traditional prenatal care were designed to decrease the risk of coronavirus exposure of patients, staff, and physicians while continuing to provide safe and comprehensive obstetric care.

Telehealth Uptake into Prenatal Care and Provider Attitudes during the COVID-19 Pandemic in New York City: A Quantitative and Qualitative Analysis.

OBJECTIVE: This study aimed to (1) determine to what degree prenatal care was able to be transitioned to telehealth at prenatal practices associated with two affiliated hospitals in New York City during the novel coronavirus disease 2019 (COVID-19) pandemic and (2) describe providers' experience with this transition. STUDY DESIGN: Trends in whether prenatal care visits were conducted in-person or via telehealth were analyzed by week for a 5-week period from March 9 to April 12 at Columbia University Irving Medical Center (CUIMC)-affiliated prenatal practices in New York City during the COVID-19 pandemic. Visits were analyzed for maternal-fetal medicine (MFM) and general obstetrical faculty practices, as well as a clinic system serving patients with public insurance. The proportion of visits that were telehealth was analyzed by visit type by week. A survey and semistructured interviews of providers were conducted evaluating resources and obstacles in the uptake of telehealth. RESULTS: During the study period, there were 4,248 visits, of which approximately one-third were performed by telehealth (n = 1,352, 31.8%). By the fifth week, 56.1% of generalist visits, 61.5% of MFM visits, and 41.5% of clinic visits were performed via telehealth. A total of 36 providers completed the survey and 11 were interviewed. Accessing technology and performing visits, documentation, and follow-up using the telehealth electronic medical record were all viewed favorably by providers. In transitioning to telehealth, operational challenges were more significant for health clinics than for MFM and generalist faculty practices with patients receiving public insurance experiencing greater difficulties and barriers to care. Additional resources on the patient and operational level were required to optimize attendance at in-person and video visits for clinic patients. CONCLUSION: Telehealth was rapidly implemented in the setting of the COVID-19 pandemic and was viewed favorably by providers. Limited barriers to care were observed for practices serving patients with commercial insurance. However, to optimize access for patients with Medicaid, additional patient-level and operational supports were required. KEY POINTS: · Telehealth uptake differed based on insurance.. · Medicaid patients may require increased assistance for telehealth.. · Quick adoption of telehealth is feasible..

A Single-Center Experience with a Pregnant Immigrant Population and Zika Virus Serologic Screening in New York City.

OBJECTIVE: Our institution is in an area of New York City with a large population of immigrants from Zika virus endemic areas. With the recent Zika virus outbreak, we sought to examine our center's experience with screening for Zika virus and outcomes among patients who tested positive for the disease during pregnancy. STUDY DESIGN: We performed a chart review of all pregnant patients who tested positive (positive serum or urine polymerase chain reaction [PCR]) or presumed positive (immunoglobulin M [IgM] enzyme-linked immunosorbent assay [ELISA] positive or IgM ELISA equivocal with positive plaque reduction neutralization test) for Zika virus. All tests were performed by the Department of Health (DOH) and followed Centers for Disease Control and Prevention guidelines in effect at the time of specimen collection. Testing of cord blood, placenta, and/or neonatal blood were/was performed by the DOH for New York County. Prenatal ultrasounds for fetal head size and surveillance for calcifications were performed by maternal-fetal medicine specialists. Infant head ultrasound results were included when available. RESULTS: Between March 2016 and April 2017, 70 pregnant patients were positive or presumed positive for Zika infection during pregnancy. Of those, 16 women had positive urine or serum PCR and the remaining 54 were presumed positive. Among positive cases, five women tested positive via urine PCR only, nine women tested positive via serum PCR only, and two women had both positive urine and serum PCR. Fifteen of 67 infants (22%) born during the study period were born to mothers with positive urine or serum PCR testing. Sixty-five newborns were clinically normal with normal head measurements. Of the intracranial ultrasound performed, one infant had a grade 1 intraventricular hemorrhage, four had incidental choroid plexus cysts, and one had severe ventriculomegaly that was also noted antenatally. There were 2 positive and 15 equivocal infant serum IgM samples and 1 positive placental PCR from these pregnancies. There were four pregnancy terminations and two cases with fetal anomalies in this population that were split evenly between patients who tested positive and those who tested presumed positive for Zika virus during pregnancy. CONCLUSION: We found no differences in pregnancy or neonatal outcomes between women who tested positive and presumed positive for Zika virus during pregnancy. Testing of infants and placenta tissue after delivery was largely inconclusive. Improvement in testing for Zika virus infection is needed to determine which pregnancies are at risk for congenital anomalies. Further research is still needed to determine which children are at risk for poor neurodevelopmental outcomes related to Zika virus and how to best coordinate care among the immigrant population during a new disease epidemic.

Later sleep timing is associated with an increased risk of preterm birth in nulliparous women.

BACKGROUND: Although uterine contractions have a diurnal periodicity and increase in frequency during hours of darkness, data on the relationship between sleep duration and sleep timing patterns and preterm birth are limited. OBJECTIVE: We sought to examine the relationship of self-reported sleep duration and timing in pregnancy with preterm birth. STUDY DESIGN: In the prospective Nulliparous Pregnancy Outcome Study: Monitoring Mothers-to-be cohort, women completed a survey of sleep patterns at 6-13 weeks gestation (visit 1) and again at 22-29 weeks gestation (visit 3). Additionally, at 16-21 weeks gestation (visit 2), a subgroup completed a weeklong actigraphy recording of their sleep. Weekly averages of self-reported sleep duration and sleep midpoint were calculated. A priori, sleep duration of <7 hours was defined as "short," and sleep midpoint after 5 am was defined as "late." The relationships among these sleep characteristics and all preterm birth and spontaneous preterm birth at <37 weeks gestation were examined in univariate analyses. Multivariable logistic regressions that controlled for age and body mass index alone (model 1) and with additional covariates (race, smoking, insurance, and employment schedule) following a backward elimination process (model 2) were performed. RESULTS: Of the 10,038 women who were enrolled, sleep survey data were available on 7524 women at visit 1 and 7668 women at visit 3. The rate of short sleep duration was 17.1% at visit 1 and 20.7% at visit 3. The proportion with a late sleep midpoint was 11.6% at visit 1 and 12.2% at visit 3. There was no significant relationship between self-reported short sleep and preterm birth across all visits. However, self-reported late sleep midpoint (>5 am) was associated with preterm birth . Women with a late sleep midpoint (>5 am) in early pregnancy had a preterm birth rate of 9.5%, compared with 6.9% for women with sleep midpoint ≤5 am (P=.005). Similarly, women with a late sleep midpoint had a higher rate of spontaneous preterm birth (6.2% vs 4.4%; P=.019). Comparable results were observed for women with a late sleep midpoint at visit 3 (all preterm birth 8.9% vs 6.6%; P=.009; spontaneous preterm birth 5.9% vs 4.3%; P=.023). All adjusted analyses on self-reported sleep midpoint (models 1 and 2) maintained statistical significance (P<.05), except for visit 1, model 2 for spontaneous preterm birth (P=.07). The visit 2 objective data from the smaller subgroup (n=782) demonstrated similar trends in preterm birth rates by sleep midpoint status. CONCLUSION: Self-reported late sleep midpoint in both early and late pregnancy, but not short sleep duration, is associated with an increased rate of preterm birth.

Association of Adverse Pregnancy Outcomes With Self-Reported Measures of Sleep Duration and Timing in Women Who Are Nulliparous.

STUDY OBJECTIVES: To examine the relationship of self-reported sleep during pregnancy with adverse pregnancy outcomes. A secondary objective was to describe the concordance between self-reported and objectively assessed sleep during pregnancy. METHODS: In this prospective cohort, women completed a survey of sleep patterns at 6 to 13 weeks' gestation (visit 1) and again at 22 to 29 weeks' gestation (visit 3). Additionally, at 16 to 21 weeks (visit 2), a subgroup completed a week-long sleep diary coincident with an actigraphy recording. Weekly averages of self-reported sleep duration and sleep midpoint were calculated. A priori, sleep duration < 7 hours was defined as "short," and sleep midpoint after 5:00 AM was defined as "late." The relationship of these sleep abnormalities with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) was determined. RESULTS: Of the 10,038 women enrolled, sleep survey data were available for 7,524 women at visit 1 and 7,668 women at visit 3. A total of 752 women also provided ≥ 5 days of sleep diary data coincident with actigraphy at visit 2. We did not observe any consistent relationship between self-reported short sleep and HDP or GDM. There was an association between self-reported late sleep midpoint and GDM (visit 1 adjusted odds ratio 1.67, 95% confidence interval 1.17, 2.38; visit 2 adjusted odds ratio 1.73, 95% confidence interval 1.23, 2.43). At visit 2, 77.1% of participants had concordance between their diary and actigraphy for short sleep duration, whereas 94.3% were concordant for sleep midpoint. CONCLUSIONS: Self-reported sleep midpoint, which is more accurate than self-reported sleep duration, is associated with the risk of GDM. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Title: Pregnancy as a Window to Future Cardiovascular Health: Adverse Pregnancy Outcomes as Predictors of Increased Risk Factors for Cardiovascular Disease, Identifier: NCT02231398, URL: https://clinicaltrials.gov/ct2/show/NCT02231398.

Predictors of sleep-disordered breathing in pregnancy.

BACKGROUND: Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES: The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN: Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS: Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION: Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.

The pattern and magnitude of "in vivo thrombin generation" differ in women with preeclampsia and in those with SGA fetuses without preeclampsia.

OBJECTIVE: We aimed to determine the differences in the pattern and magnitude of thrombin generation between patients with preeclampsia (PE) and those with a small-for-gestational-age (SGA) fetus. METHODS: This cross-sectional study included women in the following groups: (1) normal pregnancy (NP) (n = 49); (2) PE (n = 56); and (3) SGA (n = 28). Maternal plasma thrombin generation (TGA) was measured, calculating: (a) lag time (LT); (b) velocity index (VI); (c) peak thrombin concentration (PTC); (d) time-to-peak thrombin concentration (TPTC); and (e) endogenous thrombin potential (ETP). RESULTS: (1) The median TPTC, VI, and ETP differed among the groups (p = .001, p = .006, p < .0001); 2) the median ETP was higher in the PE than in the NP (p < .0001) and SGA (p = .02) groups; 3) patients with SGA had a shorter median TPTC and a higher median VI than the NP (p = .002, p = .012) and PE (p < .0001, p = .006) groups. CONCLUSIONS: (1) Patients with PE had higher in vivo thrombin generation than women with NP and those with an SGA fetus; (2) the difference in TGA patterns between PE and SGA suggests that the latter group had faster TGA, while patients with PE had a longer reaction, generating more thrombin. This observation is important for the identification of a subset of patients who might benefit from low molecular-weight heparin.

Tissue factor activity in women with preeclampsia or SGA: a potential explanation for the excessive thrombin generation in these syndromes.

OBJECTIVE: The aim of this study was to determine whether the activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the plasma of women with preeclampsia (PE) and small for gestational age (SGA) neonate differ from that of normal pregnant women and whether they are related to specific placental lesions. METHODS: This cross-sectional study included the following groups: (1) normal pregnancy (n = 68); (2) PE (n= 128); and (3) SGA (n = 56). Maternal plasma TF and TFPI activity was determined with chromogenic assays. RESULTS: (1) The median maternal plasma TF activity, but not TFPI activity, differed among the study groups (p < .0001 and p = .4, respectively); (2) patients with PE had a higher median maternal plasma TF activity than women with normal pregnancies (p < .0001) and mothers with SGA fetuses (p = .002); (3) among patients with PE, those with distal villous hypoplasia had a higher median maternal TF activity than those without these placental lesions (p = .018); and (4) following adjustment for confounding variables, maternal plasma TF and TFPI activity were not associated with an SGA neonate. CONCLUSIONS: Plasma TF activity is higher in women with PE than in those with SGA or normal pregnancies. We propose that these changes may be responsible, at least in part, for the increased in-vivo thrombin generation observed in this obstetrical syndrome.